The manufacture of compositions of matter which contain viable cells, entrapped in permeable media, has been shown to be important in various fields, such as diabetes therapy, cancer treatment, and stem cell maintenance. In this regard, see, e.g., Reissue 40,555; U.S. Pat. Nos. 7,838,291; 6,818,230; 6,808,705; 6,303,151; 6,224,912; 5,888,497; and 5,643,569, and published patent application 2007/0071732, all of which are incorporated by reference in their entirety.
The processes for making these compositions of matter, hereafter referred to as “encapsulates,” has been essentially the same, regardless of the type of cell used. After isolation or securing of the cells of interest, these are suspended in an aqueous solution of an agent such as agarose, collagen, or combinations of such, or placed on a material such as gelatin sponge. When aqueous solutions are used, semi-solid beads containing the cells of interest are formed by placing the suspension in mineral oil. If gelatin sponge is used, the product, containing the cells, is rolled into a sphere, after which agarose is poured onto it, to form a bead.
The beads are then contacted to a solution of agarose, in, e.g., a Teflon spoon. The beads roll in the mixture, to form what are referred to in the art cited supra as agarose-coated macrobeads.
The initial teachings as shown by, e.g., RE 40,555 and U.S. Pat. No. 5,888,497 which teach encapsulation of secretory cells, such insulin producing islets and cancer cells, have been followed by improvements, including the encapsulation of stem cells, as shown by U.S. Pat. No. 7,838,291 and via improvements in materials used, as seen in, e.g., published patent application 2007/0071732; however, there is an ongoing need to improve the methodology for making these useful materials.
One improvement, which is very desirable in this field, is the ability to automate what is a manual process.
In the course of automating the process of manufacture, the inventors have developed special tools, which facilitate the manufacturing process. In addition, they have found that in finishing the process via placing the macrobeads in a vessel of mineral oil at a temperature gradient, one can produce macrobeads with more uniform shape and even texture than was believed possible.
How this is accomplished will be seen in the disclosure, which follows.